This proposal is concerned with the study of a synthetic approach to the naturally occurring heliangolides ciliarin, budlein A, lychnophorolide A, and eremantholide A. Some of these compounds have been found to show significant activity against cells derived from human carcinoma of the nasopharynx (KB). All of these compounds but eremantholide A contain two electrophilic moieties, i.e., a double bond in conjugation with a 3(2H)-furanone ring and an alpha-methylene lactone, that are capable of covalent binding to nucleic acids and enzymes. The proposed approach involves alkylation of a chiral tetrahydrofuranone lithium enolate, obtainable from D-mannose, with a chiral gamma-lactone containing an iodoisprepenyl group at the beta-position and a protected hydroxymethyl group trans to it at the gamma-position. 1,3-Asymmetric induction should cause the alkylation product to have the correct stereochemistry at C- 6, C-7, and C-10 of the natural products. After appropriate transformations, the initial alkylation product should yield a molecule containing an iodomethyl group at the gamma-position of the lactone ring and a 3(2H)-furanone moiety convertible into a linearly conjugated dienolate upon deprotonation with a strong base. Cycloalkylation at the gamma-position of the dienolate should allow the closure of the ten-membered carbocyclic ring and the production of a product that upon ozonolysis of an exocyclic double bond would yield a ketone containing the heliangolide ring skeleton. Conversion of this system into the target natural products should be relatively straightforward although it involves several steps.